title: A new tumor vaccine: FAPτ-MT elicits effective antitumor response by targeting indolamine2,3-dioxygenase in antigen presenting cells.
abstract: Indolamine2, 3-dioxygenase (IDO) is expressed in tumor antigen presenting cells (APCs) and plays an important role in tumor immune tolerance. Inhibiting its activity may break tumor immune tolerance and thus promote therapeutic effects. Thus, a specific inhibitor of IDO, 1-methyl-tryptophan (1-MT), is being used more and more frequently in anti-tumor studies. However, IDO also maintains systemic immune balance by suppressing abnormal immune responses. Therefore, targeting IDO in tumor-associated APCs in a way that does not disrupt immune balance warrants further investigation. In this study, we developed a new tumor vaccine, FAPτ-MT, which was produced by conjugating 1-MT to a tumor associated antigen, fibroblast activation protein α (FAPα). The results in vitro confirmed that 1-MT could be dissociated from the FAPτ-MT vaccine and inhibit intracellular IDO activity. In an FAPα-positive tumor model, the FAPτ-MT vaccine elicited an anti-tumor response which was similar to systemic treatment with the FAPτ vaccine plus 1-MT. Most importantly, administration of the FAPτ-MT vaccine did not lead to pregnancy failiure in mice carrying allogeneic fetuses. These findings that FAPτ-MT breaks tumor immune tolerance as a local IDO inhibitor, suggest that conjugation of 1-MT to a tumor antigen peptide is a potentially effective clinical cancer immunotherapy.
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Yi
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Zeng
authors.forename: Si-Chao
authors.initials: SC
authors.lastname: Huang
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Fang
authors.forename: Guan-Min
authors.initials: GM
authors.lastname: Jiang
authors.forename: Xian-Zhang
authors.initials: XZ
authors.lastname: Bu
authors.forename: Shao-Hui
authors.initials: SH
authors.lastname: Cai
authors.forename: Jun
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000201:enzymology* / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D010450:Endopeptidases; D005260:Female; D005298:Fertility / Q000276:immunology; D018093:Gelatinases / Q000276:immunology; D007108:Immune Tolerance; D007167:Immunotherapy; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000201:enzymology* / Q000276:immunology*; D011247:Pregnancy; D012697:Serine Endopeptidases / Q000276:immunology; D023041:Xenograft Model Antitumor Assays; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D019496:Cancer Vaccines; D010450:Endopeptidases; D018093:Gelatinases; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha